Abstract

Background: Screening for latent tuberculosis infection (LTBI) remains a concern in endemic regions for anti-TNF eligible patients and recent researches have shown peculiarities between the inflammatory arthropathies such as different groups of spondyloarthritis (SpA). Objectives: To evaluate the long-term efficacy of LTBI screening and treatment in patients with ankylosing Spondylitis (AS) and Psoriatic arthritis (PsA) receiving TNF blockers in a single center. Methods: A total of 218 SpA patients (135 aS and 83 aPS) were screened for LTBI before receiving anti-TNF (infliximab, adalimumab, etanercept, certolizumab pegol and golimumab) treatment using the tuberculin skin test (TST), chest X-ray (CXR) and history of previous exposure to tuberculosis (TB). Patients were regularly followed every 2-3 months and asked about infectious symptoms or new exposure. TST was not repeated regularly. LTBI patients were treated with isoniazid (300 mg/day) for 6 months, according local guidelines. Results: One hundred and eight patients (49.5%) were treated with a single anti-TNF agent and the total duration of biological treatment was approximately six years (5.9 ± 4.0). InF and aDA were most often used among the 422 treatment cycles analyzed, representing 45% and 30% respectively. LTBI screening was positive in 82 patients (38%): 69 (84%) were TST-positive, 23(28%) had a history of TB exposure and 5(6%) had an abnormal CXR. As isolated variables TST positivity and previous exposure accounted for 58(71%) and 11 (13%) LTBI diagnosis. There were some distinct patterns between aPS and aS patients screening: despite aPS patients had more cases of previous TB than aS patients (6% vs 0.7%, P= 0.03), they had a lower frequency of LTBI (30% vs 42%, P = 0.04). Among LTBI patients, TST positivity was lower in SpA than aS patients (64% vs 93%, P = 0.002), even with more previous exposure (52% vs 18%, P = 0.02) and in patients with peripheral arthritis (27% vs 42%, P = 0.03). During follow-up, 11 patients developed active TB: 5 under aDA, 5 under inF and 1 under ETA treatment. Five cases (45%) were extrapulmonary: 3 pleural, 1 peritoneal and 1 spondylodiscitis. Four (36%) cases occurred in patients with a positive LTBI screening and 7 in patients without LTBI. There was no difference in drug survival according to type or class of anti-TNF, disease subgroups, duration or use of synthetic drugs and prednisone. Four (36.3%) cases occurred in the first year, median 5.3 (1.2-8.8) months after initiating anti-TNF exposure, 2 of them (50%) in patients with positive LTBI. Seven cases were probably due to re-exposure since occurred later, median 21.9 (14.2-42.8) months (5 in patients with negative LTBI screening). Six patients (54.5%) re-initiated treatment with ETA. Only the patient who developed pulmonary TB under ETA had a second TB infection after 18 months of therapy. Conclusion: Despite the adequate screening and treatment of LTBI, according to local guidelines, TB still occurs in spondyloarthritis patients under anti-TNF therapy, even in the first year of treatment. These data point to LTBI screening/treatment failure, maybe to due to anergy, mainly in PsA patients, with peripheral disease, low adherence or re-exposition in an endemic environment. The high frequency of extrapulmonary disease is also a diagnostic challenge.

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